TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2182	6769;6770;6771	chr2:178775167;178775166;178775165	chr2:179639894;179639893;179639892
N2AB	2182	6769;6770;6771	chr2:178775167;178775166;178775165	chr2:179639894;179639893;179639892
N2A	2182	6769;6770;6771	chr2:178775167;178775166;178775165	chr2:179639894;179639893;179639892
N2B	2136	6631;6632;6633	chr2:178775167;178775166;178775165	chr2:179639894;179639893;179639892
Novex-1	2136	6631;6632;6633	chr2:178775167;178775166;178775165	chr2:179639894;179639893;179639892
Novex-2	2136	6631;6632;6633	chr2:178775167;178775166;178775165	chr2:179639894;179639893;179639892
Novex-3	2182	6769;6770;6771	chr2:178775167;178775166;178775165	chr2:179639894;179639893;179639892

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-11
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4035
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
D/V	None	None	1.0	D	0.838	0.671	0.719514389011	gnomAD-4.0.0	1.59085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85683E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
D/A	0.6198	likely_pathogenic	0.5998	pathogenic	-0.285	Destabilizing	0.99	D	0.672	neutral	D	0.576731901	None	None	N
D/C	0.9651	likely_pathogenic	0.9637	pathogenic	-0.227	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/E	0.6281	likely_pathogenic	0.6052	pathogenic	-0.422	Destabilizing	0.998	D	0.459	neutral	D	0.601594974	None	None	N
D/F	0.9762	likely_pathogenic	0.9764	pathogenic	0.137	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
D/G	0.539	ambiguous	0.5256	ambiguous	-0.573	Destabilizing	0.23	N	0.383	neutral	D	0.683424923	None	None	N
D/H	0.8073	likely_pathogenic	0.8054	pathogenic	0.181	Stabilizing	1.0	D	0.789	deleterious	D	0.645656152	None	None	N
D/I	0.9439	likely_pathogenic	0.9448	pathogenic	0.455	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
D/K	0.9316	likely_pathogenic	0.9306	pathogenic	-0.048	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
D/L	0.9276	likely_pathogenic	0.9271	pathogenic	0.455	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
D/M	0.9654	likely_pathogenic	0.9648	pathogenic	0.516	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
D/N	0.188	likely_benign	0.179	benign	-0.504	Destabilizing	0.999	D	0.689	prob.neutral	N	0.514848004	None	None	N
D/P	0.8255	likely_pathogenic	0.7924	pathogenic	0.233	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
D/Q	0.9059	likely_pathogenic	0.8987	pathogenic	-0.391	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
D/R	0.952	likely_pathogenic	0.9515	pathogenic	0.258	Stabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
D/S	0.3921	ambiguous	0.375	ambiguous	-0.658	Destabilizing	0.992	D	0.603	neutral	None	None	None	None	N
D/T	0.7196	likely_pathogenic	0.7067	pathogenic	-0.424	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
D/V	0.8443	likely_pathogenic	0.8455	pathogenic	0.233	Stabilizing	1.0	D	0.838	deleterious	D	0.597318984	None	None	N
D/W	0.9939	likely_pathogenic	0.9942	pathogenic	0.323	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
D/Y	0.8061	likely_pathogenic	0.8161	pathogenic	0.38	Stabilizing	1.0	D	0.832	deleterious	D	0.72254606	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.